Common Name(s): L-arginine is known by the names Arginine and L-arginine.
L-arginine is classed as a non-essential amino acid, however it may be regarded essential or semi-essential under stressful conditions, when L-arginine synthesis is impaired. Due to its antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic qualities, L-arginine has been examined for usage in cardiovascular illness as well as renal disease, diabetes, cystic fibrosis, sickle cell disease, and erectile dysfunction. Moreover, its immunostimulatory actions and prospective advantages in ocular diseases and preeclampsia have been assessed.
L-arginine dosing for a number of disorders has been researched using various dosages and treatment periods; current daily dosage trends range from 6 to 30 g orally in 3 split doses. Oral and intravenous (IV) preparations have been the subject of the majority of research.
No contraindications have been discovered. Nevertheless, L-arginine is contraindicated after acute myocardial infarction.
L-arginine supplementation has demonstrated favorable effects in hypertensive and preeclamptic women. L-arginine should only be taken in these populations if prescribed by and under the supervision of a health care professional, due to the paucity of research on its safety and efficacy during pregnancy and lactation.
Nitrates: Patients concurrently taking L-arginine supplements and nitrates should exercise caution. L-arginine may enhance the effects of isosorbide mononitrate and other nitric oxide donors, including glyceryl trinitrate (often known as nitroglycerin) and sodium nitroprusside. Insulin: Patients taking insulin concurrently with L-arginine should exercise caution, as the effects on insulin are uncertain. Those utilizing cholesterol-lowering medicines concurrently with L-arginine should exercise caution; the effects of cholesterol-lowering therapies are unknown.
Use of L-arginine has been associated with nausea, diarrhea, dyspepsia, palpitations, headache, and numbness. Higher doses may cause a bitter taste. Due to the vasodilatory effects of L-arginine, hypotension may ensue. The high chloride content of IV formulations containing L-arginine hydrochloride may raise the risk of metabolic acidosis in individuals with electrolyte abnormalities. In patients with renal and/or hepatic dysfunction, hyperkalemia and elevated serum urea nitrogen (BUN) values are possible.
Nitric oxide in high amounts is considered harmful to brain tissue.
Around 80% of arginine is derived from protein ingestion and protein breakdown. The remaining arginine is produced endogenously from scratch by the kidneys. 2017 for Morris Meats (e.g., shellfish, pig), milk and milk products, chocolate, watermelon, legumes (e.g., soybeans, chickpeas), oats and wheats, and nuts are sources of the amino acid arginine (eg, peanuts, walnuts). McNeal 2016 Proteins are hydrolyzed enzymatically or chemically to produce L-arginine, their physiologically active form. From gelatin hydrolysate, arginine can be precipitated in the laboratory. L-arginine can also be produced from L-ornithine and cyanamide in the presence of barium hydroxide in an aqueous solution. Budavari 1989 As L-arginine may be produced endogenously from L-citrulline, it is not a necessary amino acid for adults. L-arginine synthesis may be reduced in youngsters and persons with specific diseases (e.g., infection, trauma) in which case L-arginine may be regarded semi-essential. Morris 2017, Schwedhelm 2008
L-arginine is often promoted as a dietary supplement with claims of cardiovascular disease benefits.
Cheng 2001 and dysfunctional erections.
Cumpanas 2009, Gentile 2009 L-arginine was initially extracted from bovine horn as the stereoisomer of arginine in the 1800s. Cheng, 2001
L-arginine (C6H14N4O2), also known as 2-amino-5-guanidino-pentanoic acid, is a conditionally necessary acid in mammals whose L-form is physiologically active.
Calabro 2014, NIH 2018 In humans, it is produced from glutamine, glutamate, and proline by the intestinal-renal axis. Morris 2017; Wu 2017 2009 The portion of the side chain nearest to the backbone is lengthy and hydrophobic, and its terminus is a complicated guanidinium group. The compound is mildly soluble in ethanol but insoluble in ethyl ether. With a pKa of 2.24, it is highly alkaline. NIH 2018
Utilization and Pharmacology
L-arginine is categorized as a non-essential amino acid, however it may be regarded necessary or semi-essential during times of stress when the capacity for endogenous arginine synthesis is surpassed, such as during periods of growth (e.g., childhood, pregnancy) or trauma (eg, liver disease, severe sepsis, wound healing, cancer).
Morris 2017, Rodríguez 2008, Wu 2009 Normal L-arginine serum concentrations range between 50 and 150 mcM. Rodríguez 2008 Vegetarians may be at risk for arginine shortage because the majority of arginine in the average American diet comes from meat and fish, which offer roughly 5.5 g daily. Cheng 2001 suggests the following metabolic and physiologic functions of L-arginine in the body: building block of proteins; precursor of nitric oxide; induction of vasodilation; synthesis of creatine; reduction in xanthine oxidase activity; induction of bone and tendon formation and skin epithelization; simulation of energy metabolism through maintenance of adenosine triphosphate levels; simulation of growth hormone and prolactin release; simulation of insul Hristina 2014 L-arginine is also essential for the elimination of ammonia from the body. Calabrò 2014
Many animal and human cells produce nitric oxide, which is involved in numerous physiological and pathological processes. Luiking L-arginine is a substrate for four enzymes as of the year 2010: nitric oxide synthases, arginases, arginine glycine amidinotransferase, and L-arginine decarboxylase. Nitric oxide and L-citrulline are produced from L-arginine metabolism by nitric oxide synthase enzymes, according to Rodrguez (2008). Rodríguez 2008, Schwedhelm Arginases convert L-arginine to L-ornithine and urea in 2008. Morris 2017, Rodríguez After oral ingestion, L-arginine is eliminated presystemically (through GI flora) and systemically (by gut and liver arginases). Schwedhelm 2008 The majority of studies support the stereospecificity of nitric oxide synthase for L-arginine. However, trial results in steroid-naive patients with asthma indicate comparable concentrations of exhaled nitric oxide when either L- or D-arginine is administered, suggesting an alternative mechanism of action.
L-arginine is a necessary amino acid for the survival of certain parasites, such as Leishmania spp., the causative agent of leishmaniasis (Chambers, 2001). Wanasen 2008
The antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic characteristics of L-arginine may have favourable impacts on cardiovascular health. Cheng, 2001,
Animal and in vitro Information
By preserving nitric oxide levels, increased L-arginine concentrations may benefit vascular disease.
Wascher 1996 Nitric oxide acted as a direct radical scavenger, reduced platelet adhesion and aggregation, and altered endothelial permeability. Brandes 2000, Wascher 1997 Nitric oxide regulated tissue factor in human microvascular endothelial cells, decreasing endotoxin- and cytokine-induced expression. Yang 2000
In a randomized clinical experiment aimed to examine the efficacy of oral L-arginine 9 g/day supplementation for 6 months after an acute ST-elevation myocardial infarction, there was no significant change in vascular stiffness or left ejection fraction. Unfortunately, 8.6% of patients in the L-arginine group died, whereas there were no deaths in the control group (P=0.01), and the study was halted. Researchers determined that L-arginine should not be administered to patients following an acute myocardial infarction and suggested that widespread atherosclerosis may worsen clinical outcome in elderly individuals. Schulman 2006
In a short trial of patients with native coronary artery disease, intramural infusion of L-arginine (6 mL of 100 mg/mL) significantly decreased neointimal volume compared to saline (25 mm³ vs. 39 mm³; P=0.049) after stent deployment. At the 6-month follow-up, individuals who received L-arginine had a considerably lower proportion of neointimal volume than those who got saline (17% [13%] vs 27% [21%]; P=0.048), indicating that L-arginine may be a viable strategy for the prevention of restenosis. Suzuki 2002
In individuals with 1- or 2-vessel coronary artery disease, intracoronary infusion of 150 mcmol/min L-arginine enhanced poststenotic coronary flow without affecting healthy arteries. In addition, the usage of angiotensin-converting enzyme inhibitors and an optimal lipid profile were related with a favorable response to L-arginine therapy. In another clinical research conducted by Lauer (2008), oral L-arginine treatment proved ineffective at increasing the bioavailability of nitric oxide in patients with coronary artery disease. Blum 2000 found that L-arginine supplementation increased exercise tolerance in angina patients. Ceremuzyński 1997
In one study, the ankle brachial index of 18 patients with chronic limb ischemia due to advanced peripheral arterial disease who underwent implantation of autologous bone marrow cells and daily administration of antioxidants and L-arginine for 6 weeks showed improvement at 3 and 12 months posttreatment. There was also an improvement in ischemic ulcers in thirteen of the eighteen patients; nevertheless, two patients required amputation of the ischemic leg. The mean maximum walking distance rose significantly at three months and was maintained until the end of the study period. Napoli A 41-year-old lady with a 35-year history of type 1 diabetes and exertional angina pectoris was diagnosed with microvascular angina in 2008
And began L-arginine supplementation with two nutritional bars containing 3.3 g of L-arginine per day. The patient reported an end to her angina attacks and an enhancement in her activity ability. Due to supplement supply concerns, L-arginine supplementation was replaced with atorvastatin 40 mg daily after eight weeks of treatment. During a week, the patient’s angina bouts returned, and after eight weeks, her activity capacity deteriorated. Restarting the L-arginine supplement resulted in the eradication of her angina symptoms, suggesting that L-arginine supplementation deserves further investigation as a viable therapy option for diabetes patients with microvascular angina. Schwartz 2003
In a trial of individuals with coronary artery disease, angina pectoris functional class IV, and prior revascularization who were receiving maximal medical therapy, L-arginine 9 g/day orally for 3 months improved angina pectoris functional class (from IV to II) in seven out of ten patients. After L-arginine was discontinued, symptoms returned to functional class IV. Blum 1999
In a 2X2 factorial design, patients who underwent coronary artery bypass grafting were randomized to receive either ten 200 mcg injections of vascular endothelial growth factor (VEGF)-165 plasmid DNA or placebo in the anterior myocardium, with oral L-arginine 6 g/day or placebo for three months. At three months, the combination of VEGF-165 and L-arginine was linked with better anterior wall perfusion relative to baseline. Ruel 2008
An intracoronary infusion of L-arginine (3,200 mcmol over 10 minutes) enhanced endothelium-dependent vascular relaxation (defined as peak coronary blood flow) to a greater extent in black patients without coronary artery disease than in matched white subjects, indicating that L-arginine supplementation may offer cardiovascular benefits in certain populations.
The year 2002 according to Houghton.
Supplementation with 700 mg of L-arginine four times daily prevented nitrate tolerance when nitroglycerin was administered transdermally continuously. Four and twenty-four hours after nitroglycerin patch administration, treadmill walking time rose significantly more than placebo (P0<05). Parker 2002
The National Heart, Lung, and Blood Institute paid for the Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) prospective, single-center, randomized, double-blind, placebo-controlled study. It is the largest study done so far to look at how L-arginine affects functional capacity in people with peripheral artery disease. 133 people with intermittent claudication were given either 3 grams of L-arginine by mouth every day or a placebo for 6 months. Those who took supplements had much higher levels of L-arginine in their blood. Even though absolute claudication distance got better for those who took L-arginine for a long time (mean improvement of 11.5%), it got better by a lot more for those who took a placebo (28.3%; P=0.024), which suggests that long-term treatment has a bad effect. This may be because arginine messes up the nitric oxide synthase pathway, which leads to a paradoxical drop in the production of nitric oxide. Wilson 2007
Showed that L-arginine made the hearts of people with severe congestive heart failure work better (CHF) Bednarz 2004, Bocchi 2000, and Wascher 1997. However, in one study of CHF patients who took L-arginine supplements, all hemodynamic variables stayed the same. In the same study, healthy controls who took L-arginine had their stroke volume and cardiac index go up. Piccirillo 2004 When given with losartan 50 mg for 2 days in a row to 9 patients with stable New York Heart Association class II or III heart failure, L-arginine 20 g IV (after the second dose of losartan) improved cardiac index and stroke volume compared to losartan alone. Koifman 2006
Low-dose L-arginine-rich blood showed a protective effect in ischemia/reperfusion injury, with less perioperative myocardial infarction and shorter stays in the intensive care unit and hospital. Kiziltepe 2004
In men with high blood pressure and type 2 diabetes, taking 1,200 mg of L-arginine and 600 mg of N-acetylcysteine twice a day for 6 months improved endothelial function by making it easier for the body to use nitric oxide. In particular, the combination decreased systolic (P<0.05) and diastolic (P<0.05) mean arterial blood pressure, total cholesterol (P<0.01), low-density lipoprotein cholesterol (P<0.005), and high-sensitivity C-reactive protein (P<0.05). It also increased high-density lipoprotein levels (P<0.05) and improved intima-media thickness during endothelial postischemic vasodilation (P<0.02). Martina 2008
Statins have been shown to make nitric oxide synthase make more of itself. The levels of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, were checked in 98 older people, and then they were given either simvastatin 40 mg/day, oral L-arginine 3 g/day, or a combination therapy for 3 weeks. Subjects with high levels of ADMA were not affected by endothelium-dependent vasodilation when they only took simvastatin. Even though L-arginine on its own was linked to improvements in endothelium-dependent vasodilation, combination therapy had a bigger effect. People with low ADMA levels had better endothelial function when they took simvastatin alone, L-arginine alone, or both. Böger 2007
Cigarette smoking causes more white blood cells to stick to endothelial cells and is linked to problems with how endothelial cells work. In one study, smokers had more adhesion between monocytes and endothelial cells than nonsmokers (46.4% [4.5%] vs. 27% [5.2%]; P<0.001). After 7 grams of L-arginine were taken by mouth, smokers’ monocyte/endothelial cell adhesion dropped to 35.1% (4%) (P=0.002). Vitamin C was not found to be reversible. Adams 1997
In many diseases, arginase levels are high, which stops the body from making nitric oxide. Researchers have suggested that the “global arginine bioavailability ratio” (GABR, which is defined as arginine/[ornithine+citrulline]) is a better way to predict the development and progression of major adverse cardiovascular events than arginine levels alone. In a study of plasma samples from 1,010 patients, those with obstructive coronary artery disease had lower levels of plasma arginine but higher levels of plasma ornithine and citrulline. This made the median GABR levels lower. Even after taking into account risk factors, high-sensitivity C-reactive protein, and creatinine clearance, GABR was still linked to obstructive coronary artery disease. Tang 2009
A meta-analysis of 11 double-blind, randomized, placebo-controlled trials (N=387) that looked at the effects of L-arginine on blood pressure in people with and without different health conditions (like high cholesterol, type 2 diabetes, coronary artery disease, and polycystic ovary syndrome), most of whom were normotensive, found that systolic and diastolic blood pressure dropped by 5.39 mm Hg and 2.66 mm Hg, There was a lot of difference between them. In studies, groups of 12 to 79 people took L-arginine orally at doses of 4 to 24 g/day (the average was 9 g/day) for 2 to 24 weeks (median, 4 weeks). When sensitivity analyses were done, none of the individual studies seemed to have had a big effect on the overall combined effect sizes. Dong 2011
The American College of Cardiology Foundation/American Heart Association Guideline for the Management of Peripheral Arterial Disease (2005/2011) says that it is not clear if L-arginine helps people with intermittent claudication (level B evidence). Anderson 2013
The disease Cystic Fibrosis
In people with cystic fibrosis, a lack of nitric oxide in the airways may make it hard for them to breathe. In a clinical study, nebulized L-arginine (18 mL of a 7% solution containing L-arginine 1.3 g) given to patients with cystic fibrosis was compared with a saline (placebo) solution given to healthy controls. Fractional exhaled nitric oxide (FENO; single-breath online measurements of lower airway nitric oxide done at a constant expiratory flow of 50 mL/min) showed that inhaled L-arginine was linked to higher levels of nitric oxide (P<0.0001). After inhaling L-arginine for 4 hours, there was a significant increase in the mean forced expiratory volume in the first second (FEV1) (P<0.0005). No change in forced vital capacity was noted. After inhalation, FENO in patients who were given nebulized saline showed a small but statistically significant improvement, but FEV1 went down. Nebulized L-arginine may be a way to help people with cystic fibrosis improve their lung function, but more research is needed. Grasemann 2006
Animal and in vitro data
Streptozotocin made rats diabetic, and when they ate L-arginine, their nerve pain got better. But L-arginine did not have any effect on glucose levels, eating a lot, or losing weight. Rondon 2017
L-arginine administration stimulates insulin secretion and enhances insulin-mediated glucose disposal, with various mechanisms suggested, including beta-cells in the pancreas take up positively charged L-arginine molecules, resulting in plasma membrane depolarization; metabolism of L-arginine by arginase yields ornithine and urea; and nitric oxide is produced from L-arginine by the enzyme nitric oxide synthase.
Cheng 2001, Tsai 2009 In one study, patients with type 2 diabetes who took 9 grams of L-arginine orally every day for a month had better insulin sensitivity in their peripheral and liver cells. No changes in body weight, glycated hemoglobin, serum potassium, diastolic blood pressure, or heart rate were demonstrated. In the L-arginine group, the systolic blood pressure went down. Piatti in 2001
In study of 144 middle-aged people with poor glucose tolerance and metabolic syndrome were given 6.4 g of L-arginine or a placebo by mouth every day for 18 months. After 18 months, the patients were followed for another 90 months to find out how often diabetes would happen in the long run. At the end of this 9-year period, there were no differences in the chances of getting diabetes. However, 40.6% of the people in the L-arginine group got diabetes, while 57.4% of the people in the placebo group did. This led to an adjusted risk ratio for diabetes (L-arginine vs. placebo) of 0.66 (95% CI, 0.48 to 0.91; P<0.02). Monti 2017
In a study of the vasodilator effects of L-arginine, coinfusion with insulin enhanced the potency of arginine, with increases in renal and ocular hemodynamic parameters observed. Dallinger 2003
Diabetes patients have low levels of L-arginine and high levels of asymmetric dimethylarginine, which slows down the process of making nitric oxide. In a double-blind, vehicle-controlled, two-period, crossover pilot study, the effectiveness of a cream with 4 mg/cm² of L-arginine on improving blood flow to the feet was tested. The topical preparation improved both flow and temperature in the feet. At first, the study was going to look at the effects after a one-week washout period, but this was found to be too short (i.e., the effect of L-arginine persisted throughout the washout period). The protocol was changed so that the effects of giving L-arginine over time could be measured. This new way of making L-arginine could be a way to treat diabetes by improving blood flow and, in the long run, reducing the microvascular problems that come with the disease. Fossel 2004 In another clinical study, 8 of 11 (73%) diabetic ulcer patients who got L-arginine 10 mM subcutaneously at the wound site healed completely. The other three patients also got better, but they had to leave the study because they were moving. Arana 2004
In a study of healthy male athletes, 0.1 g/kg of arginine powder (L-arginine 45.5%) in 150 mL of water raised glucose and insulin levels 15 and 30 minutes after exercise. During the 30-minute and 45-minute recovery periods after exercise, the level of free fatty acids went down. Tsai 2009
The Endothelium Dysfunction
Endothelial function was looked at in a study of people with acute leukemia who took L-arginine supplements. Patients either got chemotherapy with anthracycline antibiotics (control group) or chemotherapy with anthracycline antibiotics plus a L-arginine IV infusion the day before and during anthracycline antibiotic administration, followed by L-arginine aspartate 5 mL three times a day for one month. L-arginine made the endothelium work better and boosted the activities of superoxide dismutase and total nitric oxide synthase. Skrypnyk 2017
Erectile TISSUE And FUNCTION
Animal and in vitro data
Nitric oxide needs to be made by L-arginine in order for smooth cavernous muscle in the penis to relax. This suggests that L-arginine may play a role in erectile dysfunction. Studies on rats found that they got an erection and that the tone of their blood vessels changed. Bivalacqua 2000 Daily L-arginine dosed at 0.65 g/kg was found to be effective in preventing radiation-induced damage to penile structures in rats. Medeiros 2014
In a controlled crossover study with men who had impotence, there was no difference between taking 500 mg of L-arginine three times a day orally and taking a placebo. Klotz 1999
L-arginine has been studied in combination with the standard of care, oral type-5 phosphodiesterase (PDE-5) inhibitors, for erectile dysfunction. Men with diabetes and erectile dysfunction were given a mix of L-arginine, nicotinic acid, and propionyl-L-carnitine (PLC) with and without the PDE-5 inhibitor vardenafil. The International Index of Erectile Function (IIEF) showed that those who took L-arginine, nicotinic acid, and PLC had better erectile function by 2 points. The IIEF score went up by 4 points in the group that only got vardenafil, and it went up by 5 points in the group that also got L-arginine, nicotinic acid, and PLC along with vardenafil. Those who were given a placebo did not get better over time. Gentile 2009 In another study, when men who didn’t respond to tadalafil 20 mg were given L-arginine 600 mg/day as an add-on therapy, their answers to two IIEF questions about their ability to get and keep an erection long enough for sexual activity got better. Cumpanas 2009
In a small (N=9) randomized, double-blind, crossover study, the effect of L-arginine supplementation on exercise performance was looked at. The men in the study ranged in age from 19 to 38 years. A 500 mL solution with 6 g of L-arginine or a placebo was given by mouth an hour before the monitored cycling machine sessions. The active and placebo treatments were separated by a 10-day washout period. When comparing L-arginine to placebo, significantly different mean ( standard deviation) values were seen for plasma nitrite levels (331198 nM vs. 159102 nM; P<0.05), systolic blood pressure (1233 mm Hg vs. 1315 mm Hg; P<0.01), and steady-state oxygen uptake (VO₂) during moderate-intensity exercise (1.480.12 L/min VO₂ slow component amplitude reduction (0.580.23 L/min vs. 0.760.29 L/min; P<0.05) and time to exhaustion (707232 seconds vs. 562145 seconds; P<0.05) were significantly better for L-arginine during severe-intensity exercise. Bailey 2010
Nutritional or Metabolic or Immunostimulatory action
Animal and in vitro data
When given to rats with jaundice, L-arginine had anabolic and immune-stimulating effects.
Kennedy 1994 It has been linked to faster healing of bone (when combined with inositol and silicon), burns, the GI tract, and tendons. It has also been linked to faster healing of pressure ulcers. Curtis in 2016, Drmic in 2017, Hristina in 2014, and Yaman in 2016
In a randomized clinical trial with people who had tuberculosis, adding arginine to chemotherapy made C-reactive protein levels and general symptoms go down after the first month of treatment. Also, after the first and second months of treatment with arginine, the body mass index (BMI) got better. Farazi 2015
When arginine-enhanced enteral nutrition was given to malnourished patients with head and neck cancer, there were fewer fistulas, shorter hospital stays, and a trend toward better survival. However, other trials were unable to show a positive clinical outcome.
De Luis 2005, De Luis 2015, van Bokhorst 2001 In a study of people who had surgery for esophageal cancer, L-arginine given by mouth as part of an immuno-enhanced diet with omega-3 fatty acids and RNA stopped the drop in platelets after surgery and lowered prothrombin activity and thrombin-antithrombin III complex levels. Also, the number of T-cells was higher in patients who took this enteral product on days 1 and 7 after surgery. So, a diet that boosts the immune system and includes L-arginine may be helpful after surgery for esophageal cancer to lower the risk of getting sick. Aiko 2008
In a randomized, double-blind pilot study, the effectiveness of L-arginine 36.2 g given by mouth was compared to that of a placebo (alanine 51.2 g) in people who were getting skin transplants as part of reconstructive surgery. When it came to angiogenesis, reepithelialization, and neutrophil count, there were no differences between the two treatment groups. Most of the patients found it hard to drink the solutions because they tasted bad, which may have changed the results given the small number of people in the study. Debats 2009 In a study done by the same researchers, IV arginine gave the same results, and there were no improvements in how quickly human skin graft donor sites healed. Debats 2011
Two randomized clinical trials that looked at the use of arginine in premature babies were found in a review of the scientific literature. Supplementing with arginine lowered the risk of necrotizing enterocolitis. This effect is thought to be caused by lower levels of nitric oxide and hypoxic-ischemic injury, which makes the mesenteric vascular resistance go up. Mitchell 2014 In these studies, arginine supplementation cut the risk of stage II and III necrotizing enterocolitis by 59% compared to a placebo (relative risk [RR], 0.41; 95% confidence interval [CI], 0.2 to 0.85; P<0.02). Also, all stages of necrotizing enterocolitis were 60% less common in people who took arginine (RR, 0.4; 95% CI, 0.23 to 0.69; P=0.001). At age 3, there were no big differences between the groups in terms of neurodevelopmental disabilities. Mitchell 2014 In another review that looked at 3 trials of arginine supplementation in neonates with necrotizing enterocolitis, the risk of stage I (RR, 0.37 [95% CI, 0.15 to 0.9]) and stage III (RR, 0.13 [95% CI, 0.02 to 1.03]) necrotizing enterocolitis was significantly lower in the arginine group than in the control group. Arginine didn’t cause any bad effects, like low blood pressure or changes in how glucose stays in the body. Shah 2017
Animal and in vitro data
L-arginine caused the posterior ciliary arteries of both rabbits and humans to relax in a way that depended on the concentration. Chuman 2017
In a randomized clinical trial that looked at the effects of giving healthy adults an infusion of 1 g/min of arginine for 30 minutes, the mean arterial pressure went down and the blood flow to the retina and choroid went up. The effects were still there 30 minutes after the infusion stopped, which suggests that arginine could help with eye diseases like diabetes or glaucoma that are linked to endothelial dysfunction. Garhöfer 2005
In a randomized clinical trial with pregnant women who had high blood pressure, an infusion of 20 g of arginine per 500 mL lowered both the systolic and diastolic blood pressure. The heart rate of the fetus was not changed. Neri 2004 In another study, women with preeclampsia who took 12 g/day of arginine by mouth for two days had no change in their mean diastolic blood pressure. Staff 2004
Animal and in vitro data
Rats with renal ischemia/reperfusion injury had less kidney damage when they were given 300 mcg/kg/min IV of L-arginine. Tong 2017
Bennett-Richards (2002) found that giving arginine to children with chronic renal failure did not improve endothelial dysfunction, and it did not protect adults with chronic renal failure from nephrotoxicity caused by contrast media. Miller 2003
Nitric oxide levels may go up in people with decompensated cirrhosis, which can cause their kidney function to get worse over time. In a prospective study done by a group of researchers, plasma levels of nitric oxide and L-arginine went up as renal function got worse. Both levels were higher in patients with hepatorenal syndrome type II. Kayali 2009
Sickle cell disease
Sickle cell disease is a lack of the amino acid arginine. In people with sickle cell disease, neutrophils that release harmful substances damage endothelial cells and make them work harder. Neutrophils cause blood vessels to close off and damage to tissues. Nitric oxide is broken down in part by the superoxide anion that endothelial cells and neutrophils give off. In a state where these cells don’t have enough L-arginine, they make more superoxide anion. Patients with sickle cell disease have a lack of L-arginine because of too much arginase activity, according to Gladwin 2003, Morris 2005, and Waugh 2001. Morris 2017
In a clinical study with 5 people who had sickle cell disease, giving them 0.1 g/kg of the L-arginine precursor L-citrulline twice a day made them feel better. Supplementation was also linked to higher levels of the amino acid arginine and lower counts of both total leukocytes and segmented neutrophils. Continuous L-citrulline therapy kept the number of white blood cells and neutrophils at lower levels. Waugh 2001
In a randomized, placebo-controlled trial, 38 sickle cell disease patients who were in the hospital for vasoocclusive crises were given L-arginine 100 mg/kg three times a day by IV or mouth, or a placebo, for 5 days or until they were released. In the group that got L-arginine, the total amount of opioids given through a vein was cut by 54%, and pain scores at discharge were lower. Supplementation didn’t have a big effect on how long people stayed in the hospital, but there was a trend in favour of treatment. Morris 2013
Ten people with sickle cell disease and pulmonary hypertension (mean age 32.715 years) who took L-arginine by mouth three times a day for five days saw their pulmonary artery systolic pressure drop by 15.2% (from 63.913 mm Hg to 54.212 mm Hg; P=0.002). Follow-up echocardiography at 1 month showed that 4 of the 9 compliant patients went back to their baseline pulmonary artery systolic pressure values, 1 patient got worse and was admitted for acute chest syndrome, and 4 patients kept getting better. Two of the patients who got better started on transfusion therapy, and one of them kept getting L-arginine therapy at 0.1 g/kg twice a day. Smith 2003
Patients with sickle cell disease were given either 0.1 to 0.2 g/kg of L-arginine three times a day or 25 to 100 mg of sildenafil three times a day. The effects on safety, cardiopulmonary function, and fetal hemoglobin were measured. L-arginine did not improve pulmonary pressure or the distance a person could walk in 6 minutes. Sildenafil, on the other hand, did. But fetal hemoglobin levels dropped by 2.9% (16.1%) from baseline in patients who took L-arginine, while fetal hemoglobin levels rose in patients who took sildenafil. Little 2009
Animal and in vitro data
Rats given L-arginine by IV at doses between 50 and 250 mg/kg were more likely to live through heatstroke (54 to 245 minutes). In particular, L-arginine lowered intracranial hypertension and raised levels of a metabolite of nitric oxide in the hypothalamus. Chen 2008 Clinical data
A Cochrane review of randomized clinical trials found that there isn’t enough evidence about the effects of nitric oxide donors, L-arginine, or nitric oxide synthase inhibitors to recommend their use in acute ischemic stroke. The only drug that has been looked at is glyceryl trinitrate. In people who have just had a stroke, glyceryl trinitrate lowers blood pressure, speeds up the heart rate, and gives them headaches, but it doesn’t change the clinical results (high-quality evidence). Bath 2017
High levels of nitric oxide are thought to be harmful to brain tissue.Bath 2017
In a clinical trial that looked at intrauterine growth restriction therapy, giving L-arginine 3 g/day orally for 20 days made newborn babies heavier than if nothing was done.
Sieroszewski 2004: L-arginine helped some people who had overdosed on valproate and also had a condition called hyperammonemia. Schrettl 2017
L-arginine has been studied for a number of conditions using different doses and lengths of treatment (up to 18 months). The most common daily doses range from 6 to 30 g taken orally in 3 separate doses.
Morris in 2017 Most of the research has been done on oral and intravenous forms. Oral L-arginine supplementation is limited by how L-arginine is taken up by the GI tract and liver, as well as the risk of GI distress, which often depends on the dose. So, L-citrulline supplements could be used to boost L-arginine levels and make nitric oxide more bioavailable. Allerton 2018
Pregnancy and Breastfeeding
A systematic review of the research (N=884 women) found that pregnant women with high blood pressure or who were thought to be at risk for preeclampsia who took L-arginine supplements were less likely to get preeclampsia.
Dorniak-2014 Wall’s Since there isn’t much known about the safety and effectiveness of L-arginine during pregnancy and breastfeeding, it should only be used in these situations if a health care provider tells you to and you’re under their care.
Nitrates: Patients who take both L-arginine supplements and nitrates need to be careful. L-arginine may make the effects of isosorbide mononitrate and other nitric oxide donors, like nitroglycerin and sodium nitroprusside, stronger. Stokes 2003
Insulin: People who take insulin and L-arginine together should be careful because the effects on insulin are hard to predict.
Cholesterol-lowering drugs: Patients who take cholesterol-lowering drugs along with L-arginine should be careful because the effects of cholesterol-lowering drugs are hard to predict.
Fleischmann 2002, Piatti 2001
There have been reports of nausea, diarrhea, dyspepsia, palpitations, headaches, and feeling numb. Morris, 2017. Enteral arginine supplementation was linked to diarrhea in a study of malnourished people with head and neck cancer. De Luis 2015 In a study evaluating effects of L-arginine 9 g/day over 6 months on exercise capacity in patients with stable angina pectoris, no adverse reactions were reported. Ceremuzyński 1997 Higher doses may be associated with a bitter taste that may affect patient compliance. Chagan 2002 Due to L-vasodilatory arginine’s properties, hypotension may occur. IV preparations with L-arginine hydrochloride have a lot of chloride, which could be dangerous for patients with electrolyte imbalances. The acidity of L-arginine can cause metabolic acidosis, which is a sudden drop in blood pH that has been linked to arrhythmias. Hyperkalemia can happen when intracellular potassium is moved out of cells. This can happen in people with liver and/or kidney problems who are being treated with L-arginine. Because of a decreased ability to get rid of urea, L-arginine therapy may cause BUN and urea to rise in people with kidney disease. Böger 2001
High levels of nitric oxide are thought to be harmful to brain tissue.
Bath 2017 A 21-month-old girl who was being tested for a lack of growth hormone got too much L-arginine by accident. She went into cardiopulmonary arrest, and 36 hours after her heart and lungs were brought back to life, she died from myelinolysis. Gerard 1997
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